crossing96/oncoscreening huggingface dataset:
Machine learning-based characterization of stemness features and construction of a stemness subtype classifier for bladder cancer.	BACKGROUND: Bladder cancer (BLCA) is a highly heterogeneous disease that presents challenges in predicting prognosis and treatment response. Cancer stem cells are key drivers of tumor development, progression, metastasis, and treatment resistance. The features and prognostic significance of stemness in bladder cancer need further investigation. METHODS: We used bladder cancer datasets from the TCGA and GEO databases, based on stemness gene sets from the StemChecker database, to identify stemness subtypes using the consensus clustering algorithm. We calculated the mRNA expression-based stemness index (mRNAsi) using the OCLR algorithm. We compared the differences in overall survival, genomic characteristics, tumor microenvironment, and treatment response between the stemness subtypes. We constructed the stemness subtype classifier using machine learning algorithms such as LASSO regression, random forest, and multivariate logistic regression. The function of the classifier gene was validated through experiments. RESULTS: We divided bladder cancer patients into two subtypes based on the enrichment scores of stemness gene sets. Patients within subtype 1 have a higher mRNAsi score, a better survival rate, an antitumor microenvironment, and higher sensitivity to immunotherapy, while patients within subtype 2 show higher aneuploidy scores, greater homologous recombination defects, an elevated tumor mutation burden, and increased chemotherapy sensitivity. We constructed a stemness subtype classifier based on six differentially expressed genes between the two subtypes. The classifier demonstrated good performance in predicting prognosis on three additional datasets from the GEO database and two non-muscle invasive bladder cancer datasets. Through tumor sphere formation experiments and western blotting, we found that TNFAIP6, out of the six classifier genes, maintains stemness. TNFAIP6 silencing also facilitated the chemotherapy response of cisplatin, docetaxel, and paclitaxel on bladder cancer cells. Furthermore, decreasing TNFAIP6 expression caused the immune checkpoint gene PD-L1 to downregulate. CONCLUSION: This study provided valuable insights into the heterogeneity of BLCA stemness, and the stemness subtype classifier may facilitate molecular classification and personalized treatment selection for BLCA patients. Besides, TNFAIP6 may serve as a potential future stemness target guiding bladder cancer chemotherapy and immunotherapy.	bladder
Unlocking the secrets: Exploring the connection between HPV and bladder cancer in Pakistan.	BACKGROUND: Human Papillomavirus' (HPV) clear association with anogenital carcinomas raises concerns about its role in urologic carcinomas due to anatomical proximity. This etiological link is under-researched in Pakistan, creating a critical gap in the literature. OBJECTIVES: To decipher any probable pathological association of high-risk HPV genotypes in bladder cancer etiology. METHODS: Bladder biopsies from 63 bladder cancer patients, confirmed by H&E and IHC staining were collected with histopathological and clinical data, after informed consent. DNA was extracted and processed for HPV detection using L1 consensus primers. HPV genotyping was performed using E6-E7 specific primers for HPV16 and 18, via conventional PCR. RESULT: About 15.9% (10/63) of bladder cancer cases were HPV-positive. 30% (3/10) of which were HPV16-positive, 60% (6/10) were HPV18-positive, while the remaining 1 sample (1/10) was neither positive for HPV16 nor 18 indicating a probable involvement of other high-risk genotypes. Histologically, most of the HPV-positive bladder cancers were low-grade invasive urothelial carcinoma, having a male-to-female incident ratio of 9:1 with an average age of 65 years. No significant association was found between HPV prevalence and tobacco consumption, physical activity, co-morbidities (diabetes and hypertension), and treatment effectiveness. CONCLUSION: The study provides the latest epidemiological data on the prevalence and genotype distribution of HPV in bladder cancer in Pakistan. Although the frequency of HPV was not so high, nonetheless an association with bladder cancer incidence was identified as an important risk factor. Consequently, HPV remains a serious issue in low- and middle-income countries (LMICs), significantly contributing to otherwise preventable cancers.	bladder
Perioperative outcomes using template mapping after radical cystectomy and extended lymph node dissection.	BACKGROUND: To evaluate oncologic and perioperative outcomes of extended pelvic lymph node dissection (PLND) during robot-assisted radical cystectomy (RARC) based on the location of lymph node positivity (LN(+)). METHODS: We reviewed a tertiary center database of patients with bladder cancer who underwent extended PLND during RARC from 2004 to 2020. Patients were assigned to a standard (sPLN(+)) or extended (ePLN(+)) cohort based on LN(+) location. ePLN(+) patients were LN(+) in one or more of the following: common iliac, presacral, aortic bifurcation, or paracaval packets. The Kaplan-Meier method estimated recurrence-free survival (RFS) and overall survival (OS). Perioperative 90-day complications were identified using the Clavien-Dindo system. RESULTS: Ninety patients were included; 43 (48%) were sPLN(+,) and 47 (52%) were ePLN(+). The median follow-up for sPLN(+) and ePLN(+) patients was 14.9 and 20.0 months, respectively. ePLN(+) patients were older than sPLN(+) patients (median age 75 vs. 68 years, p = 0.019). There were more ≤ cT1 LN(+) patients in the sPLN(+) cohort compared to the ePLN(+) cohort (26% vs. 9%, p = 0.037). We recorded no differences in 90-day mortality or in RFS or OS between baseline and 12-year follow-up between groups (all, p > 0.05). Overall, the grade II or higher complication rate was 71%, with similar rates for the sPLN(+) and ePLN(+) (77% vs. 66%, p = 0.26) cohorts. CONCLUSION: Location of LN(+) does not affect oncologic outcomes in patients who underwent extended PLND. This underscores the lack of a notable therapeutic benefit beyond the standard dissection template. CLINICAL TRIAL NUMBER: Not applicable.	bladder
Phases of tight junction barrier disruption during transurothelial migration of invasive urothelial cancer cells.	Bladder cancer is characterised by its multifocal nature and a high recurrence, yet the underlying mechanisms of these phenomena remain only partially understood. In the present study, we aimed to investigate transurothelial invasion of urothelial cancer cells as a potential mechanism for dissemination of bladder cancer and to identify the key molecules involved in urothelial barrier disruption. Using confocal and electron microscopy, we were able to show that within a 24-hour timeframe muscle-invasive urothelial cancer cells T24 adhere to the partially differentiated normal urothelial in vitro model and initially cause localised disruption of the tight junctions between urothelial cells. Subsequently, urothelial cells separate and individual T24 cells migrate paracellularly through the urothelium. qPCR analysis identified fibroblast activation protein (FAP)/seprase as the candidate most likely to be involved in urothelial barrier disruption. In addition, treatment of T24 cells with Pefabloc resulted in the inhibition of T24 cell invasion. Our results contribute to the understanding of the mechanisms underlying transurothelial invasion of urothelial cancer cells. Among the molecules tested, FAP/sepraseis likely involved in cancer cell-induced disruption of the urothelial barrier, suggesting its potential as a therapeutic target to prevent progression and recurrence of bladder cancer.	bladder
Loss of chromosome Y is unrelated to the composition of the tumor microenvironment and patient prognosis in muscle-invasive urothelial bladder cancers.	BACKGROUND: Loss of chromosome Y (LOY) has recently been proposed to be associated with cancer aggressiveness, altered T-cell function, and poor prognosis in bladder carcinomas. METHODS: Chromosome Y was analyzed using fluorescence in-situ hybridization on a tissue microarray containing 2,071 urothelial carcinomas of the urinary bladder from male patients, including 487 patients who had undergone cystectomy for muscle-invasive disease and for whom follow-up data were available. Data on tumor microenvironment were obtained from a previous study. RESULTS: LOY was found in 26.0% of 1,704 analyzable cancers. In non-invasive cancers, LOY frequency was comparable in pTa G2 (22.8%) and pTa G3 (24.1%, p = 0.8036) carcinomas and slightly increased from pTa to pT2 - 4 carcinomas (23.1% for pTa and 27.2% for pT2 - 4) but these differences were not significant (p = 0.0794). In muscle-invasive cancers, LOY frequency slightly increased from pT2 (25.5%) to pT4 cancers (33.0%), but this association was not significant (p = 0.1814). Among pT2 - 4 cancers, LOY was associated with venous invasion (p = 0.0010) but unrelated to pT, pN, and L-status, as well as to overall, recurrence-free, and cancer-specific survival. Muscle-invasive urothelial carcinomas with and without LOY did not show significant differences in the number of CD8 positive lymphocytes, fraction of CD8 positive intraepithelial lymphocytes, number of macrophages and dendritic cells, and fraction of T helper and T regulatory cells. CONCLUSION: The lack of a clear association of LOY with histopathological parameters of cancer aggressiveness, patient prognosis, and parameters describing the tumor microenvironment strongly argues against the driving role of LOY in bladder cancer progression and cancer-associated immune reactions.	bladder
DLEU2 facilitates bladder cancer progression through miR-103a-2-5p/SOS1 axis.	BACKGROUND: Bladder cancer (BC) represents a life-threatening malignancy within the urinary system. Dysregulated long non-coding RNAs (lncRNAs) play pivotal roles in the advancement of BC. LncRNA deleted in lymphocytic leukemia 2 (DLEU2) is implicated in the development of various cancers. However, its role and regulatory mechanisms in BC remain unclear. This research aimed to explore the expression, biological function, and molecular mechanisms of DLEU2 In BC progression. METHODS: Expression profiles of lncRNAs, microRNAs (miRNAs), and mRNAs in normal and BC tissues were examined by leveraging the raw data sourced from the NCBI GEO database. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) validated expression levels in BC cells. To evaluate the proliferation and migration capabilities of BC cells, assays such as CCK-8, EdU, Transwell, and scratch were carried out. Luciferase reporter assays examined interactions between DLEU2 and miR-103a-2-5p and between miR-103a-2-5p with SOS1. Protein expression of SOS1 in BC cells was analyzed via western blotting. RESULTS: DLEU2 was markedly increased in BC tissues. Functionally, DLEU2 overexpression elevated BC cell proliferation and migration, while its knockdown produced the opposite effects. Mechanistically, DLEU2 acted as a molecular sponge for miR-103a-2-5p, which targeted SOS1. miR-103a-2-5p knockdown enhanced proliferation and migration, while co-knockdown of miR-103a-2-5p and DLEU2 reversed these effects. Overexpression of SOS1 also promoted proliferation and migration, which were counteracted by miR-103a-2-5p overexpression. Conversely, SOS1 knockdown inhibited these processes, with miR-103a-2-5p knockdown reversing this inhibition. CONCLUSIONS: These findings demonstrate that DLEU2 facilitates BC progression via the miR-103a-2-5p/SOS1 axis. This study reveals a novel regulatory mechanism underlying BC development and highlights DLEU2 as a potential therapeutic target for BC treatment.	bladder
Protein disulfide isomerase-enriched extracellular vesicles from bladder cancer cells support tumor survival and malignant transformation in the bladder.	Bladder cancer (BC) patients face high rates of disease recurrence, partially driven by the cancer field effect. This effect is mediated in part by the release of pro-tumorigenic cargos in membrane-enclosed extracellular vesicles (EVs), but the specific underlying mechanisms remain poorly understood. Protein disulfide isomerase (PDIA1) catalyze disulfide bond formation and can help mitigate endoplasmic reticulum (ER) stress, potentially supporting tumor survival. Here, BC cells were found to exhibit better survival under ER stress when PDIA1 was downregulated. These cells maintained homeostatic PDIA1 levels through the EV-mediated release of PDIA1. Chronic exposure of urothelial cells to these PDIA1-enriched BCEVs induced oxidative stress and DNA damage, ultimately leading to the malignant transformation of recipient cells. The EV-transformed cells exhibited DNA damage patterns potentially attributable to oxidative damage, and PDIA1 was found to be a key tumorigenic cargo within EVs. Tissue microarray analyses of BC recurrence confirmed a significant correlation between tumor recurrence and the levels of both PDIA1 and ER stress. Together, these data suggest that cancer cells selectively sort oxidized PDIA1 into EVs for removal, and these EVs can, in turn, induce oxidative stress in recipient urothelial cells, predisposing them to malignant transformation and thereby increasing the risk of recurrence.	bladder
Contribution of lesion shape features to the VI-RADS for predicting muscle invasion in bladder tumors.	OBJECTIVE: Muscle invasion in bladder cancer is a crucial factor influencing treatment decisions and prognosis. We hypothesize that the integration of tumor shape characteristics with the VI-RADS scoring system improves the predictive accuracy for assessing muscle invasion in bladder cancer. METHODS: This prospective observational study included patients scheduled for transurethral resection of bladder tumor (TURBT) and/or cystectomy due to suspected bladder cancer between March 2022 and November 2024. All patients underwent multiparametric bladder MRI following the VI-RADS protocol. Tumor segmentation was performed using 3D Slicer to assess shape features, including sphericity, surface area, surface-volume ratio, elongation, and flatness. Mann-Whitney U tests were conducted to evaluate the association between shape features and muscle invasion, while ROC (Receiver Operating Characteristic) analysis determined threshold values. RESULTS: The study included 119 patients (98 males, 21 females; mean age 66.9 ± 9.9 years, range 33-89). Using VI-RADS ≥ 3 as the threshold, sensitivity was 100 %, with a specificity of 65.91 %. For VI-RADS ≥ 4, sensitivity was 80.65 %, and specificity was 95.45 %. A significant relation was found between tumor sphericity and muscle invasion. For VI-RADS ≥ 3B, sensitivity was 100 %, and specificity was 66.67 %. CONCLUSION: The VI-RADS algorithm demonstrated high predictive accuracy for muscle invasion, particularly for tumors scored VI-RADS ≥ 4. Additionally, while a relation was identified between tumor sphericity and muscle invasion, its incorporation into the VI-RADS scoring system did not enhance the overall predictive performance of the algorithm.	bladder
High-glucose-associated YTHDC1 lactylation reduces the sensitivity of bladder cancer to enfortumab vedotin therapy.	Hyperglycemia is a recognized risk factor for bladder cancer (BC). Enfortumab vedotin (EV), the first NECTIN4-targeting antibody-drug conjugate, demonstrates promising clinical efficacy in patients with advanced BC. In this study, we show that EV treatment is less effective in BC patients with diabetes than in those with normoglycemia. The subsequent in vitro and in vivo experiments indicate that high glucose decreases the sensitivity of BC cells to EV. Mechanistically, lactate overproduction associated with high glucose promotes AARS1-mediated YTHDC1 lactylation and enhances RNF183-mediated YTHDC1 ubiquitination. Downregulated YTHDC1 reduces JUND mRNA stability in an m(6)A-dependent manner, subsequently decreasing NECTIN4 expression and EV responsiveness. Our study identifies a high-glucose-associated lactate-AARS1-YTHDC1-JUND-NECTIN4 axis that affects EV sensitivity in BC. Targeting this axis with JUND activators or β-alanine may offer therapeutic strategies to enhance the sensitivity of BC cells to EV.	bladder
Chromatin accessibility states affect transrenal clearance of plasma DNA: Implications for urine-based diagnostics.	BACKGROUND: Urinary cell-free DNA (ucfDNA) is a valuable resource for truly non-invasive liquid biopsy. UcfDNA comprises transrenal ucfDNA passing from the bloodstream through the glomeruli and locally shed urinary-tract ucfDNA. Understanding their differences in characteristics may enable new diagnostic applications. METHODS: We analyzed 136 ucfDNA samples from healthy controls, pregnant women, patients with chronic kidney diseases (CKDs), and bladder cancer using massively parallel sequencing. Fragmentomic characteristics including fragment sizes and 5' end motifs were deduced. The relationship between ucfDNA and chromatin accessibility was examined by overlapping ucfDNA with open chromatin regions (OCRs, lacking histones) and heterochromatin regions (HCRs, tightly packed with histones). FINDINGS: Compared with urinary-tract ucfDNA, the transrenal ucfDNA was shorter and enriched for C-ends. The transrenal ucfDNA was over-represented in OCRs but depleted in HCRs, indicating an interplay between the glomerular filtration barrier and the effective cfDNA size. In patients with proteinuria (preeclampsia and CKDs), the amount of ucfDNA from HCRs increased, suggesting elevated glomerular permeability of histone-bound plasma DNA molecules. In oncology, the use of hypomethylation signals in HCRs enhanced bladder cancer detection, with an area under the receiver operating characteristic curve of 0.93. CONCLUSIONS: Chromatin accessibility states impact the transrenal clearance of plasma DNA, likely through the size restriction of the glomerular barrier. This realization has enabled the rational development of novel approaches for detecting or monitoring renal dysfunction and urological cancers. FUNDING: The Innovation and Technology Commission of the Hong Kong SAR Government (InnoHK initiative) and the Li Ka Shing Foundation supported this study.	bladder
Comparative Genomic Characterization of Small Cell Carcinoma of the Bladder Compared With Urothelial Carcinoma and Small Cell Lung Carcinoma.	PURPOSE: Small cell bladder cancer (SCBC) is a rare histologic variant of bladder cancer with an aggressive disease course and poor outcomes. Given its uncommon nature, there is a paucity of high-quality data characterizing genomic drivers of this disease, and most patients are treated with approaches mirroring small cell lung cancer (SCLC). Leveraging the Tempus Lens deidentified clinically annotated genomic data set, we sought to evaluate the mutational landscape of SCBC relative to urothelial carcinoma (UC) and SCLC. METHODS: Somatic pathogenic genomic alterations in patients with SCBC, UC, and SCLC of any stage who underwent blood- or tissue-based genomic profiling through the Tempus assay were cataloged. Baseline clinical and demographic features were compared across histologic groups. Alterations were collated and summarized using descriptive statistics. Pairwise comparisons were performed to assess differences in mutation frequency across pathologic cohorts. RESULTS: In total, 149 SCBC, 4,350 UC, and 1,697 SCLC patients were included in the study. The most common genomic alterations in SCBC were in TP53 (87%), TERT (75%), and RB1 (70%). Among SCBC patients with TP53 mutations, RB1 comutations were observed in 77% of patients. Compared with UC, SCBC patients were significantly enriched for TP53, RB1, KMT2D, and KDM6A mutations. Compared with SCLC, SCBC patients were enriched for TERT, ARID1A, and CREBBP mutations, among others (P < .05). Multiple clinically targetable mutations were observed in SCBC, including PIK3CA (19%), ERBB2/3 (13%), and ALK (10%). Limitations of this study include its retrospective nature. CONCLUSION: This study represents one of the most extensive efforts to characterize SCBC to date, providing a novel understanding of the genomic alterations underlying the disease and revealing actionable mutations that could serve as potential targets for improved clinical outcomes.	bladder
Management of Patients with Muscle-Invasive Bladder Cancer Achieving A Clinical Complete Response after Neoadjuvant Therapy: Evidence and Consideration for Active Surveillance.	PURPOSE OF REVIEW: To review the landscape of bladder preservation management and active surveillance for those who achieve clinical complete response to neoadjuvant chemotherapy. RECENT FINDINGS: Multiple cohorts of patients with clinical complete response report overall survival rates over 80% multiple years after treatment without cystectomy. Most recently, prospective clinical trials have been pursuing clinical complete response as a valid primary endpoint. Recent advances in immunotherapy and molecular biomarkers present new horizons in expanding the potential patient population as well as accuracy in prediction of pathologic complete response. While neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for muscle-invasive bladder cancer, interest in active surveillance is growing as evidenced by the increasing number of studies. Accumulating evidence and new prospective data suggest this could be a plausible option in the future. These cohorts remain highly selected, thus generalizability is still under investigation.	bladder
Comparison of hyperthermic intravesical chemotherapy using pirarubicin and Bacillus Calmette-Guérin in the treatment of patients with high-risk non-muscle-invasive bladder carcinoma: a retrospective study.	PURPOSE: To evaluate and compare the effectiveness and safety of hyperthermic intravesical chemotherapy (HIVEC) utilizing pirarubicin (THP) and Bacillus Calmette-Guérin (BCG) in the treatment of individuals diagnosed with high-risk non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: This study was a retrospective study that combined a review of medical records with an outcomes management database. A total of 48 patients who received HIVEC with THP and 43 patients who received BCG treatment following transurethral resection of bladder tumors (TURBT) were found between January 2017 and December 2020. Recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were evaluated. RESULTS: The baseline features of the HIVEC group (n = 48) and the BCG group (n = 43) were evenly matched. The median duration of follow-up was 61.0 ± 14.5 months. RFS at 1, 2, 3, 4, and 5 years of the BCG group and the HIVEC group were (90.76%, 76.54%, 58.07%, 51.14%, 45.05% vs. 98.04%, 79.53%, 62.46%, 55.93%, 50.03%, p = 0.58). PFS at 1, 2, 3, 4, and 5 years were (97.77%, 85.85%, 81.01%, 74.26%, 67.36% vs. 100.00%, 89.57%, 83.05%, 76.68%, 73.68%, p = 0.53). OS at 1, 2, 3, 4, and 5 years were (100.00%, 100.00%, 90.64%, 88.47%, 83.43% vs. 100.00%,100.00%,97.81%, 96.08%, 90.40%, p = 0.45). The overall incidence and severity of AEs related to the therapy were comparable in both groups. CONCLUSION: HIVEC with THP offered a satisfactory safety profile and similar effectiveness to BCG. Our findings suggest that it may be regarded as a viable supplementary treatment for high-risk NMIBC patients when there is a shortage of BCG.	bladder